Mammals have a remarkable ability to detect submillisecond differences in the arrival times of sounds at the two ears. These interaural time differences (ITDs) are a primary cue for sound localization. The earliest stage of the mammalian auditory pathway in which ITDs are computed is the medial superior olive (MSO). A conspicuous feature of MSO electrophysiology is the auditory neurophonic: large, stimulus-evoked local field potentials. While the neurophonic has been observed since early studies of the auditory brain stem over half a century ago, its precise relationship to MSO neural activity remains largely unknown. The proposed research will advance knowledge of binaural hearing by identifying how MSO neurons generate the neurophonic and how the neurophonic may participate in sound localization processing in the MSO. The specific aims of the proposed research are (1) to accurately predict the auditory neurophonic response to monaural and binaural stimuli using computational, biophysically-based models; (2) to infer physiological properties of MSO neurons from the neurophonic; and (3) to determine the extent to which the neurophonic promotes binaural processing by enhancing coincidence detection in MSO neurons. The proposed research will use biophysically-detailed computational models of MSO neurons to simulate neural activity and the neurophonic; intracellular and extracellular voltages in a population of MSO neurons will be coupled and solved simultaneously. Simulation results, in conjunction with experimental data provided by a collaborator, will provide new insight in to essential physiological properties of MSO neurons. Furthermore, simulation studies will illustrate how the neurophonic influences coincidence detection in MSO neurons. This is an ideal system for studying local field potentials and their possible influence on neural activity because potentials in the auditory brain stem are large (a few mV) and MSO neurons perform a well-studied and temporally precise neural computation (coincidence detection to code for sound localization). The proposed research will advance knowledge of MSO physiology, aid the interpretation of experimental data, guide future experimental studies of the MSO, and provide a systematic analysis of the effect of local field potentials on neural activity. The proposed research focuses on field potentials in the MSO, but we expect that the research will inform studies of local field potentials in other brain regions and other organisms. PUBLIC HEALTH RELEVANCE: The proposed research will investigate extracellular field potentials in the medial superior olive, a brain stem nucleus that is essential for sound localization. By developing and using biophysically-based computational models to simulate these field potentials, the proposed research will elucidate how medial superior olive neurons generate these field potentials and how the extracellular potentials may participate in the temporally precise computations performed by the medial superior olive. The project supports the mission of the NIDCD to support biomedical research and research training in the normal processes of hearing.